(409f) Liposome and Polyelectrolyte Layers Derived Single Shot Vaccine Platform for Controlled Release of Inactivated Chikungunya Virus

Immunization through inactivated virus enhances the safety profile of the vaccine and is one of the most efficient technique to protect against infectious diseases. However, inactivated vaccines require multiple rounds of vaccinations that often lead to missing or mistimed doses thereby limiting their potency. This multidose requirement further limits mass immunization during the outbreak of an infectious disease such as chikungunya virus (CHIKV) in a place without herd immunity. Single shot vaccines capable of releasing the antigen intermittently can potentially be employed to overcome the shortcomings of multi-dose vaccines and provide herd immunity in shorter period of time. A sustained release of antigen can help in maintaining high concentration of antibodies in the system and programmed delayed release can induce strong booster effect. In this study, we engineered a single shot vaccine delivery platform comprising liposomes (LNP) embedded polyelectrolyte multilayer (PEM) lattice to provide controlled spatiotemporal release of CHIKV antigen and thus induce long term immunity. The CHIKV virus inactivated using γ-radiations in presence of MDP complex (MDP-iCHIKV) was injected in mice and tested for production of antibodies. The MDP-iCHIKV were then encapsulated in LNP followed by embedment in PEM films so as to obtain a programmed release of antigen at different time points. We performed the characterization of LNP and LNP-PEM assembly using dynamic light scattering method to determine the size and zeta potential measurements to determine the surface charge. Further confocal imaging and scanning electron microscopy was conducted to analyze the structure properties of the LNP-PEM assembly. Analysis of encapsulation and released CHIKV antigen concentration was performed using ELISA. In-vivo studies were performed by injecting the LNP-PEM assembly in mice followed by quantification of anti-CHIKV IgG in serum at different time points. The studies showed that MDP complex protected CHIKV viral envelop proteins while destruction of its genome by γ-radiation and also induced anti-CHIKV IgG response upon injection in mice. Significant changes in size, charge and structural properties were observed in the process of LNP embedment into PEM thus confirming the intended design of the vaccine plaform . We obtained about 75% encapsulation efficiency of CHIKV antigen in LNP and nearly 80% adhesion efficiency of LNP on PEM. In-vivo studies showed patterned increase and decrease in production of anti-CHIKV IgG indicating towards intermittent release of antigen from the LNP-PEM assembly. We are further working on optimizing the design of this single-shot vaccine platform to achieve a programmed release of antigen at multiple stages. We believe that this design for single shot vaccine platform would not only eliminate the need for multiple booster shots for inactivated vaccines but can also be potentially employed for long term immunization against a variety of pathogens.